a section of a rat brain is imaged in dull green. a much brighter green human organoid takes up a large portion of the left side of the brain.
a section of a rat brain is imaged in dull green. a much brighter green human organoid takes up a large portion of the left side of the brain.

Researchers Transplant Human Neurons into Rat Brains

The human cells, engineered to respond to blue light, influenced rat behavior when stimulated.

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Katherine Irving

Katherine Irving is an intern at The Scientist. She studied creative writing, biology, and geology at Macalester College, where she honed her skills in journalism and podcast production and conducted research on dinosaur bones in Montana. Her work has previously been featured in Science.

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ABOVE: A human organoid glows bright green inside a section of a rat brain. Stanford University

For the first time, researchers have successfully transplanted human neurons into the brains of baby rats, they report today (October 12) in Nature. The human cells formed connections with rat neurons and could be used to control the rats’ behavior.

“It’s a very important . . . very cool study,” Yun Li, a molecular geneticist at the University of Toronto who was not involved in the research, tells MIT Technology Review. “The fact that they succeeded in many of these experiments is quite extraordinary.”

To perform human cell experiments, especially when studying the effects of certain drugs, scientists have developed models called organoids: tiny structures grown from stem cells that mimic the human brain or other organs. However, they can’t replicate the complexity of real human neuron development on their own, Science News reports.

See “Organoids Don’t Accurately Model Human Brain Development

In a bid to further organoid development, scientists transplanted human cerebral organoids into the brains of days-old rat pups whose immune systems were tamped down so as not to reject the human cells. By using young rats rather than adults, the researchers hoped the cells would be integrated more smoothly and form more connections in the rats’ brains. Indeed, they report, the human neurons matured successfully, growing six times larger than neurons grown in a dish and forming connections with rat neurons via synapses. “They’re just absolutely immense,” Stanford University neuroscientist and lead author Sergiu Pașca tells Technology Review. “The cells have just moved to another level of maturation.”

See “Sergiu Pasca Builds Brains to Study Developmental Disease

To test whether the transplanted human neurons could affect the young rats’ behavior, Pașca and the other researchers genetically altered the human cells using a technique called optogenetics, which allows cells to respond to light. They then used a fiber optic cable to shine a blue light on the rat-integrated human neurons whenever they provided the rats with water. The rats rapidly began to associate the shining of the light with water: After just two weeks, they began to lick in anticipation of drinking when the light was shone.

See “How Manipulating Rodent Memories Can Elucidate Neurological Function

The study has brought up ethical questions regarding the treatment of animals.

“I do not think that it is ever—ever—ethically justified to treat animals as resources humans can exploit for human advantage,” Taimie Bryant, a professor of animal law at the University of California, Los Angeles, tells New Scientist. “It seems to me that rats’ consciousness as it is, without human manipulation, is rather remarkable and that damaging a rat’s brain is emblematic of an attitude towards nature that imperils human and non-human animals’ prospects for continued life on Earth.” Other experts voiced concern that the changes to the rat brain could open the door to advanced cognition in the lab animals. “It raises the possibility that you’re creating an enhanced rat that might have cognitive capacities greater than an ordinary rat,” Julian Savulescu, a bioethicist at the National University of Singapore, tells Technology Review.

The rats in this study didn’t show any evidence of advanced cognition or human behavior, Pașca tells Technology Review. Regardless of ethical concerns, he believes work like this could significantly advance drug development and help tackle complicated human disorders, he tells Science News. “Challenging disorders will require bold approaches,” he says. “We will need to build human models that recapitulate more aspects of the human brain to study these uniquely human conditions.”